Murine Kupffer cells (KC) were isolated by a high yield collagenase perfusion technique. The morphology, surface markers, and secretory products were typical of macrophages in other tissues. However, KC released negligible levels of H2O2 and O-2, in contrast to peritoneal macrophages. KC oxygen consumption was not increased by agents triggering a respiratory burst in peritoneal cells. Moreover, KC capacity to secrete reactive oxygen intermediates (ROI), in contrast to Ia antigen expression, was not enhanced by exposure to lymphokines or recombinant gamma interferon. The selective defect in KC oxidative response was paralleled by impaired in vitro killing of Toxoplasma gondii trophozoites and Leishmania donovani promastigotes and amastigotes. Deficient secretion of ROI by KC might protect hepatocytes and erythrocytes from injury during endocytosis by KC, but might render the liver more susceptible to parasitization by organisms that are primarily killed through oxygen-dependent mechanisms.

Sublethal infection of mice with Listeria monocytogenes was accompanied by an influx of immigrant macrophages into the liver and the generation of substantial H2O2 by isolated liver macrophages. H2O2 production paralleled the course of infection and, after resolution of granulomata, returned to the low levels seen in normal livers. To assess the activation status of Kupffer cells and immigrant macrophages in listeriosis, a separation protocol was developed based on the differential adherence properties of the two macrophage populations. As in the steady state, Kupffer cells in listeriosis failed to generate significant levels of H2O2 and did support the replication of internalized toxoplasmas. Immigrant macrophages produced substantial levels of H2O2 and could quantitatively account for H2O2 production by total liver macrophages. Our findings suggest distinct functions for Kupffer cells and immigrant macrophages.

Surface antigen profiles of Leishmania donovani promastigote isolates have been studied. Surface patterns of Brazilian and African isolates display remarkable similarities and are extremely simple, consisting of three major peptides of 65,000, 25,000, and 23,000 mol wt. Surface iodination and biosynthetic labeling coupled to immunoprecipitation techniques revealed that a single major determinant of 65,000 mol wt is recognized in all strains by sera from kala-azar patients from both Brazil and Africa. This major determinant is not brought down by sera from normal individuals and shows no significant cross-reactivity with sera from Chagas' disease, leprosy, or syphilis patients. Binding to concanavalin A suggests a glycoprotein nature for this antigen. Sera from patients with cutaneous leishmaniasis (L. braziliensis) also recognized the same 65,000-mol wt determinant, although to a lesser extent. The possibility that this major surface antigen is shared, with minor differences, not only by L. donovani strains but between Leishmania species in general is suggested.

No abstract

Parenteral administration of the potent hepatocarcinogen N-hydroxy-2acetylaminofluorene to rats results in a substantial inhibition of hepatic RNA polymerase III(C), the enzyme responsible for the synthesis of tRNA and 5 S RNA. The minor component of RNA polymerase I11 extractable from nuclei shows a 45-65% reduction in activity while the major component of the enzyme extractable from cytoplasm shows a 40-65% inhibition. This reduction of RNA polymerase I11 activity is sufficient to account for the inhibition of rRNA synthesis produced by administration of the carcinogen in vivo. 1